1. Field of the Invention
This invention relates to a protein having amino acid sequence in SEQ ID No.:1 of the Sequence Listing derived from MP52. The invention also relates to a homodimer protein of said protein and a pharmaceutical composition for treating cartilage and bone diseases containing the dimer protein as an active ingredient. The invention also relates to a process for preparing the above described protein in a large amount and with a high purity by culturing E. coli which was transformed with a plasmid containing a DNA sequence capable of expressing the above described protein. The invention further relates to a method for treating cartilage and bone diseases, which comprises administering to a human a pharmaceutical composition containing, as an active ingredient, an effective amount of the homodimer protein.
2. Description of the Prior Art
Pharmaceutical compositions comprising vitamin D3, calcitonin, estrogen or their derivatives as well as bisphosphonate derivatives have been used in clinical practice for preventing and treating bone diseases. Recently, bone morphogenetic protein (BMP hereinafter), the TGF-β gene superfamily comprising BMP-2 through BMP-9 and related proteins, have been reported to have bone morphogenetic activity.
Furthermore, the bone morphogenetic activity of one of those proteins called MP52 has been also reported (WO 93/16099 and WO 95/04819). A mature region of MP52 protein is considered to be a protein consisting of 120 amino acid residues having the N-terminal alanine, and its amino acid sequence is described in these publications.
A protein called GDF-5, having an analogous amino acid sequence with MP52, is also described in Nature, vol. 368, p. 639-643 (1994) and WO 94/15949.
However, these proteins can not be easily prepared in a purified form on an industrial scale.
Mammalian cell lines such as L-cells have been tried on for producing MP52 with genetic engineering technology. However, it has been found not easy to prepare MP52 in a purified form and in a high yield with the expression systems.